Phosgene is a significant environmental hazard which produces pulmonary edema of unknown etiology. These studies on reactions of phosgene with specific functional and from exposure to this toxic agent. The specific aims, therefore are: (1) Assessment of pulmonary biochemical lesions as expressed by a) changes in surfactant synthesis, secretion, turnover, and surface activity b) effects on energy metabolism c) plasma membrane structural enzymic derangements and d) effects on collagen synthesis and degradation. (2) Localization of these biochemical lesions to specific pneumocyte species in the terminal bronchiolar - alveolar or other anatomical regions. Attempts will be made through studies of phosgene exposure effects on whole lungs and cultured pneumocytes to define specific cellular, organelle, enzymatic, and macromolecular lesions of this gas. We will attempt to define through ultrastructural tracer studies, the exact site and route of fluid leakage from the vasculature. The principal methodologies of the proposed research are enzyme kinetics, techniques of cell biology applied to whole lung and pneumocytes in culture, and physiochemical properties of pulmonary surfactant and plasma membrane fractions. The overall goal of this research is to define the primary etiologic factors in phosgene pathology and, thereby, to provide information which may allow treatment of the underlying lesions. The proposed studies are also important because they provide a framework for study of other environmental toxic agents which may affect the lungs and because they promise to yield information which may be applicable to investigation of basic mechanisms involved in the development of pulmonary edema.